The objective of the proposed research is the elucidation of the general biochemistry and primary structure of the major gene products coded for by the H-2 complex, which is the major histocompatibility complex(MHC) of the mouse. Specifically, plasma membrane glycoproteins coded for by the I region (immune response region), and by the K region of the H-2 complex, will be examined. Aspects of the general objective which will be pursued for the Ia antigens (I region associated antigens), are determination of the molecular basis of serological heterogeneity of these antigens, and correlation of I region immune functions with Ia antigen structure. In addition, radiochemical methods including amino acid sequencing, ion exchange chromatography of tryptic fragments, and limited enzymic and chemical digestions will be used to determine some aspects of the structure of the Ia antigens. Preliminary studies on the H-2K "classical" transplantation antigen will include the purification of this gene product on a radiochemical scale. Later studies will be directed at large scale purification and sequencing of the H-2K antigens from two independent haplotypes which have a cross-reactive gene products. The results of these experiments should make it possible to determine the structural basis of the H-2K antigenic determinants. When the two sets of studies are considered together, the results should give some understanding of the general structural parameters of the H-2 coded membrane glycoproteins, of the structural determinants of antigenic sites of these molecules, and of the basis of the extreme polymorphism of the products of the H-2 complex.